Regulation of casein kinase I epsilon and casein kinase I delta by an in vivo futile phosphorylation cycle

Casein kinase I delta (CKIdelta) and casein kinase I epsilon (CKIepsilon) have been implicated in the response to DNA damage, but the understanding of how these kinases are regulated remains incomplete. In vitro, these kinases rapidly autophosphorylate, predominantly on their carboxyl-terminal exten...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-06, Vol.273 (26), p.15980
Main Authors: Rivers, A, Gietzen, K F, Vielhaber, E, Virshup, D M
Format: Article
Language:English
Subjects:
3T3 Cells
Adenosine Triphosphate - metabolism
Animals
Casein Kinases
Cells, Cultured
Enzyme Inhibitors - pharmacology
Escherichia coli
HeLa Cells
Homeostasis
Humans
Isoenzymes - metabolism
Marine Toxins
Mice
Okadaic Acid - pharmacology
Oxazoles - pharmacology
Phosphoprotein Phosphatases - antagonists & inhibitors
Phosphorylation
Protein Kinases - metabolism
Rats
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Summary:Casein kinase I delta (CKIdelta) and casein kinase I epsilon (CKIepsilon) have been implicated in the response to DNA damage, but the understanding of how these kinases are regulated remains incomplete. In vitro, these kinases rapidly autophosphorylate, predominantly on their carboxyl-terminal extensions, and this autophosphorylation markedly inhibits kinase activity (Cegielska, A., Gietzen, K. F., Rivers, A., and Virshup, D. M. (1998) J. Biol. Chem. 273, 1357-1364). However, we now report that while these kinases are able to autophosphorylate in vivo, they are actively maintained in the dephosphorylated, active state by cellular protein phosphatases. Treatment of cells with the cell-permeable serine/threonine phosphatase inhibitors okadaic acid or calyculin A leads to rapid increases in kinase intramolecular autophosphorylation. Since CKI autophosphorylation decreases kinase activity, this dynamic autophosphorylation/dephosphorylation cycle provides a mechanism for kinase regulation in vivo.
ISSN:0021-9258
DOI:10.1074/jbc.273.26.15980